Expanding the therapeutic landscape: ezetimibe as non-statin therapy for dyslipidemia

Korean J Intern Med. 2023 Nov;38(6):797-809. doi: 10.3904/kjim.2023.243. Epub 2023 Oct 20.

Abstract

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density lipoprotein cholesterol (LDL-C) levels. However, it can be challenging to achieve optimal LDL-C goals with statin monotherapy. Ezetimibe, a cholesterol absorption inhibitor, offers a potential non-statin therapy to optimize LDL-C management. Key clinical trials, such as IMPROVE-IT and RACING, have demonstrated that the addition of ezetimibe to statin therapy leads to further decreases in LDL-C or significant decreases in major adverse cardiovascular events (MACEs), particularly in patients with high ASCVD risk. Subsequent meta-analyses and clinical trials have further supported the beneficial effect of ezetimibe, suggesting additive decreases in LDL-C and MACEs, as well as pleiotropic effects. This review provides a comprehensive analysis of the clinical implications of ezetimibe for managing dyslipidemia; it also evaluates the available evidence that supports the role of ezetimibe as an adjunct non-statin therapy for long-term use. However, the long-term pleiotropic effects of ezetimibe remain controversial because of limited clinical data. Therefore, additional research is needed to clarify its potential benefits beyond LDL-C reduction. Nonetheless, an understanding of the role of ezetimibe in dyslipidemia management will help clinicians to develop effective treatment strategies.

Keywords: Atherosclerosis; Cardiovascular disease; Dyslipidemias; Ezetimibe.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents* / adverse effects
  • Cholesterol, LDL
  • Drug Therapy, Combination
  • Dyslipidemias* / diagnosis
  • Dyslipidemias* / drug therapy
  • Ezetimibe / adverse effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Treatment Outcome

Substances

  • Ezetimibe
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol, LDL
  • Anticholesteremic Agents